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Covid-19: Possible Role of Neutrophil Extracellular Traps (NETSINCOVID)

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ClinicalTrials.gov Identifier: NCT04412382
Recruitment Status : Recruiting
First Posted : June 2, 2020
Last Update Posted : July 8, 2020
Sponsor:
Information provided by (Responsible Party):
Chiara Mozzini, Azienda Ospedaliera Universitaria Integrata Verona

Brief Summary:

The process by which neutrophils expel DNA together with various proteins to the outside, forming a network structure called Neutrophil Extracellular Traps (NETs) constitutes a particular cell death that involves the destruction of the nuclear membrane before the plasmatic one. This process is called NETosis and differs from other known forms of cell death, such as necrosis and apoptosis.

This process, however, if exaggerated, brings local or systemic damage. Viruses are known for their ability to evade the body's immune response. Only recently has it been seen that they can act as triggers for NETosis process.

In fact, many viruses can stimulate neutrophils to produce NETs. Virus-induced NETs can begin to circulate in an uncontrolled manner, leading to an extreme systemic response of the body with the production of immunocomplexes, cytokines, Interferon I etc.

To date, there are no data in the literature on the role of NETs in Covid-19 infection, a viral infection that leads to highly lethal interstitial pneumonia and for which there is currently no vaccine or specific therapy.

Advanced forms of Covid-19 are often characterized by hyperinflammation ("cytokine storm") with the development of an ARDS-like condition. Furthermore, reports of micro and macro thrombotic phenomena such as microangiopathy, pulmonary embolism (which has led to a careful evaluation procedure for antithrombotic prophylaxis and/or coagulation in Covid-19 patients) are increasingly frequent.

The primary objective of the study is to understand if NETs can be implicated in the response to Covid-19 and by which mechanisms. Concrete therapeutic proposals could derive from the knowledge and enhancement of this form of innate immunity.

To do this, it will be necessary to evaluate the activity of NETosis in Covid-19 patients and evaluate whether the clinical course of the disease (worsening vs healing) determines the degree of NETosis activity. Therefore, the association between mortality from Covid-19/survival and NETs activity will be studied.

Secondary objectives concern the possibility of studying the associations among NETosis markers and blood inflammation markers and among NETosis markers and the onset of peripheral or deep vein thrombosis.

Finally, the possibility that the plasma deriving from Covid-19 patients could trigger the NETosis process in vitro will be evaluated.


Condition or disease Intervention/treatment
Covid-19 Diagnostic Test: NETosis markers

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 100 participants
Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration: 1 Year
Official Title: Covid-19: Possible Role of Neutrophil Extracellular Traps
Actual Study Start Date : June 1, 2020
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2021

Group/Cohort Intervention/treatment
covid-19
Study population: Covid-19 patients aged ≥ 18 years admitted to the Covid sections of the Verona University Hospital. Based on the ongoing epidemic emergency and the lack of specific therapy, we believe that to date this should be the only INCLUSION CRITERION.
Diagnostic Test: NETosis markers

NETosis markers (Cf-DNA. MPO-DNA, Cit-H3) and the cytokines IL-6 and IL-1β will be analyzed from the subjects' plasma.

Spittle sample (or bronchoalveolar fluid if necessary for diagnostic-therapeutic purposes) will be collected and the detection of NETs at electron microscopy will be assessed.


control
Control group: medical doctors and nurses working in the University Hospital of Verona without known autoimmune diseases nor cancer.
Diagnostic Test: NETosis markers

NETosis markers (Cf-DNA. MPO-DNA, Cit-H3) and the cytokines IL-6 and IL-1β will be analyzed from the subjects' plasma.

Spittle sample (or bronchoalveolar fluid if necessary for diagnostic-therapeutic purposes) will be collected and the detection of NETs at electron microscopy will be assessed.





Primary Outcome Measures :
  1. NETOSIS AND MORTALITY [ Time Frame: 1 year ]
    correlation among plasma levels of NETosis markers and Covid-19 mortality

  2. NETOSIS AND DCOVID-19 SEVERITY [ Time Frame: 1 year ]
    correlation among plasma levels of NETosis markers and disease severity (that is duration of hospitalization in days and any need for passage to intensive care with non-invasive ventilation or intubation);


Secondary Outcome Measures :
  1. NETOSIS AND INFLAMMATION [ Time Frame: 1 year ]
    correlation among plasma levels of NETosis markers and clinical inflammation biomarkers (white blood cells, PCR IL-6-IL-1β)

  2. NETOSIS AND VENOUS THROMBOSIS [ Time Frame: 1 year ]
    correlation among plasma levels of NETosis markers and the onset of deep vein thrombosis and / or the increase in D-dimer values.


Biospecimen Retention:   Samples Without DNA
serum


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Study population: Covid-19 patients aged ≥ 18 years admitted to the Covid sections of the Verona University Hospital.

Control group: medical doctors and nurses worìking in the University Hospital of Verona.

Criteria
  • Covid-19 patients aged ≥ 18 years admitted to the Covid sections of the Verona University Hospital.
  • Control group: medical doctors and nurses working in the University Hospital of Verona.

Exclusion Criteria:

  • age <18 years;
  • pregnancy;
  • known autoimmune diseases.

For the control group:

- positivity to Covid-19 swabs and / or the presence of IgM and IgG antibodies (sierological picture known from the samples taken by the Health surveillance System of the hospital).


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04412382


Contacts
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Contact: CHIARA MOZZINI, MD-PhD +39 0458124262 chiara.mozzini@univr.it
Contact: DOMENICO GIRELLI, MD-PhD +39 0458124262 domenico.girelli@univr.it

Locations
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Italy
Univeristy of Verona Recruiting
Verona, Italy, 37136
Contact: chiara mozzini, MD PhD    +390458124262      
Sponsors and Collaborators
Azienda Ospedaliera Universitaria Integrata Verona
Investigators
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Study Chair: DOMENICO GIRELLI, MD-PhD Universita di Verona
Publications:
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Responsible Party: Chiara Mozzini, Principal Investigator, Azienda Ospedaliera Universitaria Integrata Verona
ClinicalTrials.gov Identifier: NCT04412382    
Other Study ID Numbers: NETS IN COVID-19
First Posted: June 2, 2020    Key Record Dates
Last Update Posted: July 8, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: study protocol and results
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: end 2020
Access Criteria: mail contact

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Chiara Mozzini, Azienda Ospedaliera Universitaria Integrata Verona:
Covid-19
neutrophil extracellular traps